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| [ Print-friendly version ] |
| Targeted radiotherapy delivered by an yttrium-90 radio-labelled Anti-CD66 monoclonal antibody with high dose melphalan compared to melphalan alone, prior to autologous stem cell transplantation for multiple myeloma |
| ISRCTN | ISRCTN11933044 |
| ClinicalTrials.gov identifier | NCT00637767 |
| Public title | Targeted radiotherapy delivered by an yttrium-90 radio-labelled Anti-CD66 monoclonal antibody with high dose melphalan compared to melphalan alone, prior to autologous stem cell transplantation for multiple myeloma |
| Scientific title | A randomised phase II clinical trial using targeted radiotherapy delivered by an yttrium-90 radio-labelled Anti-CD66 monoclonal antibody with high dose melphalan compared to melphalan alone, prior to autologous stem cell transplantation for multiple myeloma |
| Acronym | Anti-CD66 |
| Serial number at source | 1 |
| Study hypothesis | To determine the efficacy of targeted radiotherapy delivered by an Yttrium-90 (90Y)-radio-labelled murine anti-CD66 monoclonal antibody, given in addition to high dose melphalan (200 mg/m^2) in terms of disease response (complete remission rate and change of serum free light chain level pre and post yttrium-90-radio-labelled anti-CD66) in patients undergoing haematopoietic stem cell transplantation (HSCT) for multiple myeloma. |
| Ethics approval | Southampton and South West Hampshire Research Ethics Committee (A) approved on the 9th January 2007. |
| Study design | Multicentre randomised non-blind phase II study |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Multiple myeloma |
| Participants - inclusion criteria |
1. Histologically or cytologically proven multiple myeloma
2. In partial remission (PR) after chemotherapy and before priming therapy for stem cell mobilisation 3. Aged greater than 18 years 4. Life expectancy of at least 24 weeks 5. World Health Organization (WHO) performance status of less than two 6. Haematological and biochemical indices (these measurements must be performed within one week prior to the patient going on study): 6.1. Haemoglobin (Hb) greater than or equal to 9.0 g/dl 6.2. Neutrophils greater than or equal to 1.5 x 10^9/L 6.3. Platelets (Plts) greater than or equal to 50 x 10^9/L 7. Any of the following abnormal baseline liver function tests: 7.1. Serum bilirubin less than or equal to 1.5 x upper normal limit 7.2. Alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) less than or equal to 2.5 x Upper Limit of Normal (ULN) 8. The following abnormal baseline renal function test: 8.1. Calculated creatinine clearance greater than or equal to 50 ml/min (uncorrected value), or 8.2. Isotope clearance measurement greater than or equal to 50 ml/min 9. No concurrent or recent (within four weeks) chemotherapy for the underlying haematological condition (excluding cyclophosphamide priming for stem cell harvest). This does not include thalidomide which is permitted 10. Although the bone marrow (BM) remission status is not important, patients must have cellularity greater than 20% 11. Patients must have sufficient stem cells in cryo-storage for two transplant procedures, this is in case graft failure occurs as a result of therapy 12. Patients must be negative for human anti-mouse antibodies (HAMA) 13. Written informed consent and the ability of the patient to co-operate with treatment and follow up must be ensured and documented 14. Female patients of child-bearing potential are eligible, provided they have a negative serum pregnancy test prior to enrolment and agree to use medically approved contraceptive precautions for four weeks prior to entering the trial, during the trial and for six months afterwards 15. Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards |
| Participants - exclusion criteria |
1. Radiotherapy (except for localised pain control), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks
2. All toxic manifestations of previous treatment must have resolved. Exceptions to this are alopecia or certain Grade one toxicities which in the opinion of the Investigator should not exclude the patient. 3. Patients with BM cellularity less than 20% 4. Patients who test positive for HAMA 5. Previous high dose therapy and autologous stem cell transplant 6. Patients in complete remission (CR) after chemotherapy and prior to autologous peripheral blood stem cell transplantation (APBSCT) 7. Pregnant and lactating women are excluded 8. Major thoracic and/or abdominal surgery in the preceding three to four weeks from which the patient has not yet recovered 9. Patients who are high medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection 10. Patients with any other condition that, in the Investigator’s opinion, would not make the patient a good candidate for the clinical trial 11. Patients known to be serologically positive for hepatitis B, C or human immunodeficiency virus (HIV) 12. History of allergy, in particular a history of allergy to rodents or rodent proteins 13. History of eczema and/or asthma 14. Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease 15. Patients unable to provide informed consent or who are unable to co-operate for reasons of poor mental or physical health 16. Less than 4 x 10^6 CD34 positive cells per kg body weight |
| Anticipated start date | 01/05/2007 |
| Anticipated end date | 30/04/2011 |
| Status of trial | Ongoing |
| Patient information material | |
| Target number of participants | 80 |
| Interventions |
There are two treatment arms comparing two transplant conditioning schedules prior to autologous stem cell rescue.
Arm A: high dose melphalan (200 mg/m^2) plus targeted radiotherapy: Patients will undergo a dosimetry assessment by way of a Indium-111 radiolabelled anti-CD66 monoclonal antibody. This will be infused for 15 minutes. Two to four weeks later patients will receive targeted radiotherapy with Yttrium-90 radiolabelled anti-CD66 monoclonal antibody infused for 15 minutes. Two weeks later patients will receive the standard pre-conditioning regimen of high dose melphalan (200 mg/m^2) prior to autologous stem cell transplantation. Arm B: high dose melphalan (200 mg/m^2) alone: No targeted radiotherapy. All patients will be followed up for 12 months post-transplant. |
| Primary outcome measure(s) | Remission status pre- and post-transplantation, as defined for multiple myeloma by the European Blood and Marrow Transplantation (EBMT) organisation. Specifically the number of patients in each arm achieving CR as defined in the EBMT response criteria; remission status up to 12 months post transplant. |
| Secondary outcome measure(s) |
1. Disease response in both arms as determined from changes in serum free light chains (in those patients in whom serum free light chains are informative), up to 12 months post-transplant
2. Disease response excluding CR rates; proportion of patients with PR, stable disease (SD), progressive disease (PD), remission duration (time to disease progression), up to 12 months post-transplant 3. Engraftment quality as determined by time to recovery of peripheral blood neutrophils to greater than 0.5 x 10^9/l, platelets greater than 50 x 10^9/l and duration of recovery for greater than 180 days post-transplant, up to four weeks post-transplant 4. The treatment related mortality (TRM) and overall survival (OS) between the two arms, up to 12 months post-transplant 5. To determine the toxicity profile of 90Y-radiolabelled anti-CD66 MAb in the context of autologous stem cell transplantation, up to 12 months post-transplant 6. Pharmacokinetics of 111-in-radiolabelled anti-CD66 MAb as determined from serial blood samples, serial planar and single photon emission computed tomography (SPECT) gamma-camera imaging of selected organs, up to day five post-infusion 7. To continue to develop a dosimetry model based on SPECT and whole body gamma camera imaging, up to day post-dosimetry 8. To assess the proportion of patients that form human anti-murine antibodies (HAMA) following exposure to anti-CD66 MAb in the context of an autologous stem cell transplant, up to 12 months post-transplant |
| Sources of funding | Leukaemia Research Fund (UK) |
| Trial website | http://ctu.soton.ac.uk |
| Publications | |
| Contact name | Dr Kim Orchard |
| Address |
Senior Lecturer and Consultant Haematologist
Department of Haematology Level C, Mailpoint 8 Southampton General Hospital Tremona Road |
| City/town | Southampton |
| Zip/Postcode | SO16 6YD |
| Country | United Kingdom |
| Tel | +44 (0)2380 794 163 |
| Fax | +44 (0)2380 794 313 |
| kho@soton.ac.uk | |
| Sponsor | Southampton University Hospitals NHS Trust (UK) |
| Address |
Research and Development Office
Mailpoint 18 Southampton General Hospital Tremona Road |
| City/town | Southampton |
| Zip/Postcode | SO16 6YD |
| Country | United Kingdom |
| Tel | +44 (0)2380 794 245 |
| Fax | +44 (0)2380 798 678 |
| christine.mcgrath@suht.swest.nhs.uk | |
| Sponsor website: | http://www.suht.nhs.uk/ |
| Date applied | 30/03/2007 |
| Last edited | 21/12/2009 |
| Date ISRCTN assigned | 22/05/2007 |
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| © 2010 ISRCTN unless otherwise stated. | |
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